Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro.

OBJECTIVE

To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro.

DESIGN AND SETTING

Prospective study in a university pediatric intensive care ward and research laboratory.

PATIENTS AND MATERIALS

Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro.

INTERVENTIONS

NO inhalation and withdrawal in patients; exposure to NO donor sodium nitroprusside (SNP) and gaseous NO in vitro.

MEASUREMENTS AND RESULTS

In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 +/- 0.24 cmH2O/torr (mean +/- SEM) to 4.90 +/- 0.26 cmH2O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 +/- 0.23 cmH2O/torr) 30 min after weaning, a significant drop after 4 h (3.72 +/- 0.17 cmH2O/ torr;p < 0.001), values restored after 12 h. In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 +/- 4.0 microM/min) than in control cells (37.6 +/- 7.0 microM/ min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 +/- 10.0 microM/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot).

CONCLUSION

In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.